Δ5-androstenes useful for promoting weight maintenance or weight loss and treatment process

ABSTRACT

A method for promoting weight control by treating a subject with a therapeutic amount of one of the Δ5-androstenes listed below to stimulate weight control without affecting appetite or inducing the synthesis of sex hormones. Δ5-Androstenes providing the desired biological activities include: 
     Δ5-Androstene-3β,7α-diol-17-one 
     Δ5-Androstene-3β-ol-7,17-dione 
     Δ5-Androstene-3β,7α,17β-triol 
     Δ5-Androstene-3β,17β-diol-7-one 
     Δ5-Androstene-3β-acetoxy-7,16,17-trione 
     Δ5-Androstene-3β,16α-dihydroxy-7,17-dione 
     Δ5-Androstene-3α-propionoxy-16β-acetoxy-7,17-dione 
     Δ5-Androstene-3β,7α,17β-triol-16-one 
     Δ5-Androstene-3β,17β-diol-7,16-dione 
     Δ5-Androstene-3β,16α,17β-triol-7-one.

This is a continuation of U.S. patent application Ser. No. 08/123,151,filed Sep. 2, 1993 which is a continuation-in-part of U.S. patentapplication Ser. No. 867,288 filed Apr. 10, 1992, now U.S. Pat. No.5,296,481, which is a continuation of U.S. patent application Ser. No.575,156 filed Aug. 29, 1990, abandoned.

FIELD OF THE INVENTION

The invention relates to the use of steroids for effecting a desiredbiological response. Specifically, the invention relates to a treatmentprogram using Δ5-androstenes for promoting weight maintenance and/orweight loss (hereinafter referenced collectively as "weight control").

BACKGROUND

The steroid dehydroepiandrosterone (DHEA) is believed to stimulatevarious biological responses including (i) inducing the synthesis ofvarious thermogenic enzymes which are effective for regulatingmetabolism and thereby promoting weight control without affectingcaloric intake, and (ii) inducing an increase in the production of thesex hormones androgen and estrogen.

The ability of DHEA to promote weight control is believed to be mediatedthrough enhanced thermogenesis (conversion of foodstuffs to heat energyrather than chemical energy such as ATP and/or triacylglycerides). Thethermogenic effect mediated by DHEA is believed to result from theability of DHEA to stimulate the synthesis of thermogenic enzymesincluding mitochondrial glycerol 3-phosphate dehydrogenase (G3P-DH) andcytosolic malic enzyme (ME). Such enzymes tend to reduce the efficiencyof energy metabolism within the body,

Unfortunately, DHEA is generally considered to be ineffective as aweight controlling therapeutic agent because the dosage necessary toachieve weight control frequently produces significant adverseside-effects including substantial increases in the concentration of sexhormones.

Accordingly, a therapeutic agent possessing the weight controlcharacteristic of DHEA without the adverse side-effect of stimulatingthe synthesis of sex hormones would be extremely useful. In addition,the effectiveness of such a therapeutic agent could be significantlyenhanced if the agent possessed an increased weight control activityrelative to DHEA.

SUMMARY OF THE INVENTION

A method for promoting weight maintenance and/or weight loss(hereinafter referenced collectively as "weight control") which includesthe step of treating a subject with an effective weight controllingamount of a Δ5-androstene which is effective for stimulating the desiredbiological response of promoting weight control while beingsubstantially ineffective for inducing the undesired biological responseof synthesising sex hormones.

Δ5-androstenes providing the desired beneficial biological responsewithout the undesired biological response include:

Δ5-Androstene-3β,7α-diol-17-one (1)

Δ5-Androstene-3β-ol-7,17-dione (2)

Δ5-Androstene-3β,7α,17β-triol (3)

Δ5-Androstene-3β,17β-diol-7-one (4)

Δ5-Androstene-3β-acetoxy-7,16,17-trione (5)

Δ5-Androstene-3β,16α-dihydroxy-7,17-dione (6)

Δ5-Androstene-3β-propionoxy-16β-acetoxy-7,17-dione (7)

Δ5-Androstene-3β,7α,17β-triol-16-one (8)

Δ5-Androstene-3β,17β-diol-7,16-dione (9)

Δ5-Androstene-3β,16α,17β-triol,7-one (10)

and derivatives thereof wherein one or more of the hydroxyl or ketosubstituents is a group convertible thereto by hydrolysis.

Examples of such hydrolyzable groups include hydroxyl groups esterifiedwith an acid selected from the group consisting of (i) normal orbranched, saturated or unsaturated C₂₋₂₂ aliphatic acids, (ii) C₇₋₁₂aromatic acids, (iii) C₃ or larger dicarboxylic acids in which only oneof the carboxyl groups is esterified to the hydroxyl group(s) on thesteroid, or (iv) inorganic acids such as sulfuric and phosphoric.

DETAILED DESCRIPTION OF THE INVENTION INCLUDING A BEST MODE

The Δ5-androstenes identified below possess a unique combination ofproperties including the ability to promote weight control withoutaffecting appetite and without stimulating the production of sexhormones.

Δ5-Androstene-3β,7α-diol-17-one (1)

Δ5-Androstene-3β-ol-7,17-dione (2)

Δ5-Androstene-3β,7α,17β-triol (3)

Δ5-Androstene-3β,17β-diol-7-one (4)

Δ5-Androstene-3β-acetoxy-7,16,17-trione (5)

Δ5-Androstene-3β,16α-dihydroxy-7,17-dione (6)

Δ5-Androstene-3β-propionoxy-16β-acetoxy-7,17-dione (7)

Δ5-Androstene-3β,7α,17β-triol-16-one (8)

Δ5-Androstene-3β,17α-diol-7,16-dione (9)

Δ5-Androstene-3β,16α,17β-triol,7-one (10)

and derivatives thereof wherein one or more of the hydroxyl or ketosubstituents is a group convertible thereto by hydrolysis.

Examples of such hydrolyzable groups include hydroxyl groups esterifiedwith an acid selected from the group consisting of (i) normal orbranched, saturated or unsaturated C₂₋₂₂ aliphatic acids, (ii) C₇₋₁₂aromatic acids, (iii) C₃ or larger dicarboxylic acids in which only oneof the carboxyl groups is esterified to the hydroxyl group(s) on thesteroid, and (iv) inorganic acids such as sulfuric and phosphoric.

These steroids may also be administered as a carbamate or other suchderivative capable of releasing the specified steroid within theintestinal tract, blood and/or body tissue. The desired biologicalactivity is a function of the steroid moiety. Derivations of a moietymay serve a variety of beneficial functions including stabilization ofthe steroid, flavoring or obscuring the natural flavor of the steroid,or affecting the rate of absorption of the steroid.

SYNTHESIS

(1) Δ5-Androstene-3β,7α-diol-17-one (7α-hydroxy DHEA)

Δ5-Androstene-3β,7α-diol-17-one (7α-hydroxy DHEA) can be synthesizedfrom commercially available DHEA acetate by sequentially synthesizing:

Δ5-androstene-3β hydroxy-17-one acetate (DHEA acetate)Δ5-androstene-3β-hydroxy-7-bromo-17-one acetate (7-Br DHEA acetate)

Δ5-androstene-3β,7α-dihydroxy-17-one diacetate (7-OH DHEA diacetate)

Δ5-androstene-3β,7α-dihydroxy-17-one (7-hydroxy DHEA)

Δ5-Androstene-3β-hydroxy-7-bromo-17-one acetate (7-bromo DHEA acetate)can be synthesized from Δ5-androstene-3β-hydroxy-17-one acetate (DHEAacetate) by reacting DHEA acetate with a brominating agent, such asdibromantin (1,3-dibromo-5,5-dimethylhydantoin) or N-bromosuccinimide.The 7-bromo DHEA acetate is unstable and must be used immediately in thenext step of the process.

The 7-bromo DHEA acetate contains an isomeric mixture of 7α-bromo and7β-bromo. The isomeric mixture, may be equilibrated to 7α-bromo DHEAacetate in accordance with the method described for equilibriating acholesterol derivative in Confalone, P. N., Kulesha, I. D., andUskokovic, M. R. Jour. Org. Chem., vol. 46, pp 1030-1032 (1981).Briefly, the isomeric mixture of 7-bromo DHEA acetate is contacted withcold anhydrous LiBr and shielded from light to convert the product froman isomeric mixture of 7α and 7β to predominently 7α.

Δ5-Androstene-3β,7α-dihydroxy-17-one diacetate (7-hydroxy DHEAdiacetate) may be synthesized from 7-bromo DHEA acetate by reacting the7-bromo DHEA acetate with a mixture of glacial acetic acid and powderedsilver acetate at room temperature in a suitable solvent, such as amixture of methylene chloride and acetone.

Δ5-Androstene-3β,7α-dihydroxy-17-one (7-hydroxy DHEA) may be synthesizedfrom 7-hydroxy DHEA diacetate by dissolving the 7-hydroxy DHEA diacetatein methanol and reacting the dissolved 7-hydroxy DHEA diacetate with anaqueous solution containing a suitable base such as Na₂ CO₃.

The synthesized 7-hydroxy DHEA may then be purified by (i) evaporatingthe methanol in vacuo, (ii) extracting the 7-hydroxy DHEA into anappropriate organic solvent such as dichloromethane, (iii) evaporatingthe organic solvent in vacuo, (iv) azeotropically drying the extractedsolids containing the 7-hydroxy DHEA with a suitable organic solventsuch as ethanol, (v) dissolving the extracted solids in acetone, andthen (vi) adding hexane to the acetone solution to produce purifiedcrystals of Δ5-androstene-3β,7α-diol-17-one (7-hydroxy DHEA).

A second crop of Δ5-androstene-3β,7α-diol-17-one (7α-hydroxy DHEA)crystals may be obtained by cooling the resultant solution below roomtemperature.

(2) Δ5-Androstene-3β-ol-7,17-dione (7-keto DHEA)

Δ5-Androstene-3β-ol-7,17-dione (7-keto DHEA) can be synthesized fromcommercially available DHEA acetate by sequentially synthesizing:

3β-acetoxy-Δ5-androstene-17-one (DHEA acetate)

3β-acetoxy-Δ5-androstene-7,17 dione (7-one DHEA acetate)

Δ5-androstene-3β-hydroxy-7,17-dione (7-one DHEA)

3β-Acetoxy-Δ5-androstene-7,17-dione (7-one DHEA acetate) can besynthesized from 3β-acetoxy-Δ5-androstene-17-one (DHEA acetate) byreacting the DHEA acetate with the oxidizing agent CrO₃ in accordancewith the procedure outlined in Fieser, L. F., Jour. Am. Chem. Soc., vol75, pp 4386-4394 (1953).

Δ5-Androstene-3β-hydroxy-7,17-dione (7-one DHEA) can be synthesized fromthe 7-one DHEA acetate and purified by employing the deesterificationand purification steps set forth above in connection with the synthesisand purification of 7-hydroxy DHEA.

(3) Δ5-Androstene-3β,7α,17β-triol (7α-hydroxy-androstenediol)

Δ5-Androstene-3β,7α,17β-triol (3) can be synthesized from commerciallyavailable androstenediol-diacetate by sequentially synthesizing:

Δ5-androstene-3β,17β-diol-diacetate (20)

Δ5-androstene-3β,17α-diol-7-bromo-diacetate (21)

Δ5-androstene-3β,7α,17β-triol-3,7,17-triacetate (22)

Δ5-androstene-3β,7α,17β-triol (3)

Δ5-Androstene 3β,17α-diol-7-bromo-diacetate (21) can be synthesized fromthe commercially available Δ5-androstene-3β,17β-diol-diacetate (20) byreacting (20) with a brominating agent, such as Dibromantin(1,3-dibromo-5,5-dimethylhydantoin) or N-bromosuccinimide. Thesynthesized 7-bromo-androstenediol diacetate (21) is unstable and mustbe used immediately.

The 7-bromo-androstenediol diacetate (21) contains an isomeric mixtureof 7α-bromo-androstenediol diacetate (21a) and 7α-bromo-androstenedioldiacetate (21b) which can be equilibrated to a 7α-bromo-androstenediol(21a) in accordance with the method described in Confalone, P. N.Kulesha, I. D., and Uskokovic, M. R. Jour. Org. Chem., vol. 46, pp1030-1032 (1981). Briefly, the isomeric mixture of7-bromo-androstenediol diacetate (21a & 21b) is contacted with anhydrousLiBr and shielded from light to convert the product from an isomericmixture of 7α and 7β to predominently 7α.

Δ5-Androstene-3β,7α,17β-triol-3,7,17-triacetate (22) may be synthesizedfrom the 7α-bromo-androstenediol diacetate (21a) by reacting (21a) witha mixture of glacial acetic acid and silver acetate in a suitablesolvent, such as a mixture of methylene chloride and acetone.

Δ5-Androstene-3β,7α,17β-triol (3) may be synthesized from the7α-hydroxy-androstenediol triacetate (22) by reacting the7α-hydroxy-androstenediol triacetate (22) in methanol with an aqueoussolution containing a suitable base such as Na₂ CO₃.

The synthesized 7α-hydroxy-androstenediol (3) may then be purified by(i) evaporating the methanol in vacuo, (ii) extracting the7α-hydroxy-androstenediol (3) into an appropriate organic solvent suchas dichloromethane, (iii) evaporating the organic solvent in vacuo, (iv)azeotropically drying the extracted solids containing the7α-hydroxy-androstenediol (3) with a suitable organic solvent such asethanol, (v) dissolving the extracted solids in acetone, and then (vi)adding hexane to the acetone solution to produce purified crystals ofΔ5-androstene-3β,7α,17β-triol (7α-hydroxy-androstenediol) (3).

A second crop of Δ5-androstene-3β,7α,17β-triol (3) crystals may beobtained by cooling the resultant solution below room temperature.

(4) Δ5-Androstene-3β,17β-diol-7-one (7-keto-androstenediol)

Δ5-Androstene-3β,17α-diol-7-one (4) can be synthesized from commerciallyavailable androstenediol-diacetate by sequentially synthesizing:

Δ5-androstene-3β,17α-diol-7-one-diacetate (41)

Δ5-androstene-3β,17α-diol-7-one (4)

Δ5-Androstene-3β,17α-diol-7-one-diacetate (41) can be synthesized fromΔ5-androstene-3β,17β-diol-diacetate (androstenediol-diacetate) (40) byreacting the androstenediol-diacetate (40) with the oxidizing agent CrO₃in accordance with the procedure outlined in Fieser, L. F. Jour, Am.Chem. Soc., vol. 75, pp 4386-4394 (1953).

Δ5-Androstene-3β,17β-diol-7-one (7-keto-androstenediol) (4) can besynthesized from androstene-3β,17β-diol-7-one-diacetate (41) andpurified by employing the deesterification and purification steps setforth above with respect to the synthesis and purification of 7α-hydroxyDHEA (1) from 7α-hydroxy DHEA diacetate.

(5) Δ5-Androstene-3β-acetoxy-7,16,17-trione

Δ5-Androstene-3β-acetoxy-7,16,17-trione (5) may be synthesized fromcommercially available DHEA acetate by sequentially converting:

    ______________________________________                                        3β-acetoxy-.increment.5-androstene-17-one   (DHEA-acetate)               to                                                                            3β-acetoxy-.increment.5-androstene-7,17-dione  (51)                      to                                                                            3β-acetoxy-17-hydroxy-.increment.5,                                                        3β-trimethylsilylacetoxy-                              20 .increment.16-androstadiene-7-one-                                                           17-hydroxy-.increment.5,.increment.16-                      trimethylsilyl ether (52a)                                                                      androstadiene-7-one                                         30%               trimethylsilyl ether (52b)                                                    70%                                                         to                                                                            3β-acetoxy-  3β                                                     trimethylsilylacetoxy-                                                                          16-phenylseleno-                                            16-phenylseleno-  .increment.5-androstene-                                    .increment.5-androstene-                                                                        7,17-dione                                                  7,17-dione (53a)                                                              (53b)                                                                         to                                                                            phenylseleno-     3β-acetoxy-16-                                         (53a)             .increment.5-androstene-                                                      7,17-dione                                                  to                                                                            3β-acetoxy-.increment.5-androstene-                                                        3β,16-diacetoxy-                                       16-phenylseleno-  .increment.5-androstene-16-                                 16-m-chlorobenzoate-                                                                            phenylseleno-7,17-                                          dione             (55)                                                        7,17-dione (54)                                                               to                                                                            3β-acetoxy-16-m                                                                            3β,16-diacetoxy-.increment.5,.increment.15-            chlorobenzoate-.increment.5,.increment.15-                                                      androstadiene-7,17-                                         dione             (57)                                                        androstadiene-7,17-dione                                                      (56)                                                                          to                                                                            3β-acetoxy-.increment.5-androstene-7,16,17-trione (5)                    ______________________________________                                    

3β-Acetoxy-Δ5-androstene-7,17-dione (51) can be synthesized from3β-acetoxy-Δ5-androstene-17-one (DHEA-acetate) by reacting DHEA-acetatewith the oxidizing agent CrO₃ in accordance with the procedure outlinedin Fieser, L. F., Jour. Am. Chem. Soc., vol. 75, pp 4386-4394 (1953).

A mixture of 70%3β-(trimethylsilyl)acetoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-onetrimethylsilyl ether (52b) and 30%3β-acetoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-one trimethylsilyl ether(52a) may be synthesized from the 3β-acetoxy-Δ5-androstene 7,17-dione(51) by reacting (51) with lithium diisopropyl amide in the presence oftrimethylchlorosilane in a suitable solvent such as tetrahydrofuran at-78° C.

3β-Acetoxy-16-phenylseleno-Δ5-androstene-7,17-dione (53a) and3β-(trimethylsilyl)acetoxy-16-phenylseleno-Δ5-androstene-7,17-dione(53b) may be synthesized from3β-acetoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-one trimethylsilyl ether(52a) and3β-(trimethylsilyl)acetoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-onetrimethylsilyl ether (52b) respectively by reacting the mixture of (52a)and (52b) with benzeneselenenyl chloride in the presence of pyridine anda suitable solvent such as tetrahydrofuran at -78° C.

The carbon silylated acetate attached to the C₃ carbon atom on the (53b)fraction of the (53) mixture may be desilylated so as to convert (53b)to (53a) within the (53) mixture by treating the (53) mixture withtetra-n-butylammonium fluoride in a suitable solvent system such asether-dichloromethane-tetrahydrofuran-water.

3β,16-Diacetoxy-Δ5-androstene-16- phenylseleno-7,17-dione (54) may besynthesized from the 3β-acetoxy-16-phenylseleno-Δ5-androstene-7,17-dione(53a) by submitting (53a) to the seleno-Pummerer reaction outlined inIkota, N.; Ganem, B. Jour. Org. Chem., vol. 43, pp. 1607-1608 (1978).Briefly, the 3β-acetoxy-16-phenylseleno-Δ5-androstene-7,17-dione (53a)is sequentially reacted with m-chloroperbenzoic acid and aceticanhydride in a suitable solvent.3β-acetoxy-Δ5-androstene-16-phenylseleno-16-m-chlorobenzoate-7,17-dione(54) is also synthesized during this reaction.

3β,16-diacetoxy-Δ5,Δ15-androstadiene-7,17-dione (57) may be synthesizedfrom 3β,16-diacetoxy-Δ5-androstene-16-phenylseleno-7,17-dione (55) byoxidative dehydrogenation. The3β-acetoxy-Δ5-androstene-16-phenylseleno-16-m-chlorobenzoate-7,17-dione(54) present with (55) produces3β-acetoxy-16-m-chlorobenzoate-Δ5,Δ15-androstadiene-7,17-dione (56)which may be separated by chromatography if desired.

3β-acetoxy-Δ5-androstene-7,16,17-trione (5) may be synthesized from the3β-acetoxy-Δ5,Δ15 androstadiene-16-m-chlorobenzoate-7,17-dione (56)and/or 3β,16-diacetoxy-Δ5,Δ15-androstadiene-7,17-dione (57) by treatingthem with triethylamine in methanol.

(6) Δ5-Androstene-3β,16α-dihydroxy-7,17-dione (7-keto-16α-hydroxy DHEA)

3β,16α-dihydroxy-Δ5-androstene-7,17-dione can be synthesized by thefollowing sequence from DHEA propionate. DHEA propionate can be made bysimple esterification of DHEA.

    ______________________________________                                        3β-propionoxy-.increment.5-androstene-17 one   (DHEA-propionate)         to                                                                            3β-propionoxy-.increment.5-androstene-7,17-dione (61)                    to                                                                            3β-propionoxy-17-hydroxy-.increment.5,.increment.16-androstadiene-       7-one trimethylsilyl ether (62)                                               to                                                                            3β-propionoxy-16α-hydroxy-.increment.5-                            androstene-7,17-dione (63)                                                    to                                                                            3β,16α-dihydroxy-.increment.5-                                     androstene-7,17-dione (6)                                                     ______________________________________                                    

3β-Propionoxy-Δ5-androstene-7,17-dione (61) (NMR set forth at tableeight) can be synthesized from 3β-propionoxy-Δ5-androstene-17-one(DHEA-propionate) by reacting the DHEA-propionate with the oxidizingagent CrO₃ in accordance with the procedure outlined in Fieser, L. F.,Jour. Am. Chem. Soc., vol. 75, pp 4386-4394 (1953).

3β-Propionoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-one trimethylsilyl ether(62) may be synthesized from the 3β-propionoxy-Δ5-androstene-7,17-dione(61) by reacting (61) with lithium diisopropyl amide in the presence oftrimethylchlorosilane in a suitable solvent such as tetrahydrofuran at-78° C.

3β-Propionoxy-16α-hydroxy-Δ5-androstene-7,17-dione (63) may besynthesized from the 3β-propionoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-onetrimethylsilyl ether (62) by oxidation with m-chloroperbenzoic acid intetrahydrofuran followed by treatment with a 1N HCl solution.

The final desired product 3β,16α-dihydroxy-Δ5-androstene-7,17-dione (6)may then be synthesized from the3β-propionoxy-16α-hydroxy-Δ5-androstene-7,17-dione (63) by treatmentwith sulfuric acid in methanol.

(7) Δ5-Androstene-3β-propionoxy, 16β-acetoxy-7,17 -dione(7-Keto-16β-acetoxy DHEA propionate)

Δ5-Androstene-3β-propionoxy-16β-acetoxy-7,17-dione (7) can besynthesized from Δ5-androstene-3β-propionoxy-16α-hydroxy-7,17-dione (63)produced in accordance with the reaction sequence set forth above. TheΔ5-androstene-3β-propionoxy-16α-hydroxy-7,17-dione is treated inaccordance with the Mitsunobu conditions set forth in Hughes, D. L.;Reamer, R. A.; Bergan, J. J.; Grabowski, E. J. J. Jour Am. Chem. Soc.,vol. 110, pp 6487-6491 to invert the configuration and acetylate the 16hydroxy group.

(8) Δ5-Androstene-3β,7α,17β-triol-16-one

Δ5-Androstene-3β,7α,17β-triol-16-one (8) can be synthesized fromΔ5-androstene-3β,16α-dihydroxy-17-one diacetate (81). TheΔ5-androstene-3β,16α-dihydroxy-17-one diacetate (81) starting materialcan be synthesized in accordance with the procedure set forth inNumazawa, M. and Osawa, Y. Steroids, vol. 32, p 519 (1978).

Δ5-Androstene-3β,16α-diacetoxy-7-bromo-17-one (82) can be synthesizedfrom the Δ5-androstene-3β,16α-diacetoxy-17-one (81) by reactingΔ5-androstene-3β,16α-diacetoxy-17-one (81) with a brominating agent,such as Dibromantin (1,3-dibromo-5,5-dimethylhydantoin). TheΔ5-androstene-3β,16α-diacetoxy-7-bromo-17-one (82) is unstable and mustbe used immediately in the next step of the process.

The Δ5-androstene-3β,16α-diacetoxy-7-bromo-17-one (82) contains anisomeric mixture of 7α-bromo and 7β-bromo isomers. The isomeric mixture,may be equilibrated to 7α-bromo in accordance with the method describedfor equilibriating a cholesterol derivative in Confalone, P. N.,Kulesha, I. D., and Uskokovic, M. R. Jour. Org. Chem., vol. 46, pp1030-1032 (1981). Briefly, the isomeric mixture is contacted with coldanhydrous LiBr and shielded from light to convert the product from anisomeric mixture of 7α and 7β to predominently 7α.

Δ5-Androstene-3β,16α-diacetoxy-7α-hydroxy-17-one (83) may be synthesizedfrom the Δ5-androstene-3β,16α-diacetoxy-7α-bromo-17-one (82) by reactingthe Δ5-androstene-3β,16α-diacetoxy-7α-bromo-17-one (82) with a mixtureof glacial acetic acid and powdered silver acetate at room temperaturein a suitable solvent, such as a mixture of methylene chloride andacetone. Also produced in this reaction is a 20% yield ofΔ5-androstene-3β,7α,16α-triacetoxy-17-one.

Δ5-Androstene-3β,7α,17β-trihydroxy-16-one (8) can be synthesized fromthe Δ5-Androstene-3β,16α-diacetoxy-7α-hydroxy-17-one (83) by dissolvingthe Δ5-Androstene-3β,16α-diacetoxy-7α-hydroxy-17-one (83) in a roomtemperature methanol solution of K₂ CO₃ and stirring the solution fortwo hours. The alkaline solution enolizes the 17-keto to form the morestable 17-hydroxy-16-one combination. TheΔ5-androstene-3β,7α,17-trihydroxy-16-one (8) may then be isolated byfiltering to remove the insoluble salt, evaporating the methanol invacuo and purifying the compound by chromatography. The steroidcrystallizes from a hot methanol/ether solution upon cooling.

(9) Δ5-Androstene-3β,17β-diol-7,16-dione

Δ5-Androstene-3β,17β-diol-7,16-dione (9) can be synthesized from3β-propionoxy-16α-hydroxy-Δ5-androstene-7,17-dione (63) by treating3β-propionoxy-16α-hydroxy-Δ5-androstene-7,17-dione (63) with a 5%aqueous sodium carbonate solution in methanol.

(10) Δ5-Androstene-3β,16α,17β-triol-7-one

Δ5-Androstene-3β,16α,17β-triol-7-one (10) can be synthesized from3β,16α,17β-triacetoxy-Δ5-androstene by reacting the3β,16α,17β-triacetoxy-Δ5-androstene with the oxidizing agent CrO₃ inaccordance with the procedure outlined in Fieser, L. F., Jour. Am. Chem.Soc., vol 75, pp 4386-4394 (1953) with subsequent hydrolysis of theacetyl groups.

Without intending to be unduly limited thereby, it is believed that thesteroids identified above may be modified without loss of biologicalactivity by esterifying one or more of the hydroxyl groups with any of avariety of organic acids and inorganic acids such as sulfuric orphosphoric acid.

TREATMENT

A subject may be treated with the steroids specified herein by any ofthe commonly accepted practices including orally or by injection. Whilemany factors affect the dose rate required to attain the desiredbiological response, treatment at a dosage rate of about 0.1 to 2 grams,preferably about 0.5 to 2 grams, of the steroid per 100 kilograms bodyweight per day should generally be effective for promoting weightcontrol. A dose rate of less than 0.1 gram per 100 kilograms bodyweightper day is generally ineffective for preventing weight gain while a doserate of greater than about 2 grams per 100 kilograms bodyweight per dayincreases the cost of treatment without providing a correspondingbenefit in performance. The optimum dose rate to be administered to asubject is case specific as the optimum dose rate depends upon severalfactors including current body composition (percent fat), the desiredeffect (weight gain maintenance versus weight loss), eating habits ofthe individual (daily caloric intake), and the like. As would beexpected, the dose rate provided to a subject for the purpose ofpromoting weight loss will be greater than that necessary to promoteweight maintenance assuming identical caloric intake under each program.

Without intending to be limited thereby, we believe that the steroidsspecified herein are metabolic intermediates along the pathway toconversion of DHEA to an ultimate metabolite(s) which is actuallyresponsible for mediating an enhanced production of thermogenic enzymessuch as glycerol 3-phosphate dehydrogenase and malic enzyme.

A subject may be treated with one of the steroids specified herein onsubstantially any time schedule. It is believed that the steroidsspecified herein are effective for promoting weight control while thesteroid itself is actively present within the body as well as while theincreased concentration of thermogenic enzyme(s) induced by the steroidremain elevated. The in vivo life expectancy of the steroids and thethermogenic enzyme(s) induced thereby is not yet fully known. However,it is believed that the steroids themselves are not stored within thebody and are removed and/or deactivated within days afteradministration. Accordingly, for optimum effectiveness, the subjectunder treatment should be treated every day or two. For reasons ofconvenience the subject under treatment may be treated less frequently,such as once a week, when less than maximum performance is acceptable.

As is apparent from the factors which affect dosage and dose rate, eachparticular subject should be carefully and frequently reviewed and thedosage and/or dose rate altered in accordance with the particularsituation.

EXPERIMENTAL

Example I

(Steroid 1)

Synthesis Δ5-Androstene-3β,7α-diol-17-one

(Step 1) Into a two liter, triple neck, round bottom flask equipped witha magnetic stirrer and a reflux condenser was placed 1000 ml hexane (b.p69°-71°), 10 grams (0.03 mmoles) DHEA acetate and 13.6 grams (0.16moles) NaHCO₃ to form a first mixture. The first mixture was placedunder a N₂ atmosphere and heated under constant agitation to reflux.Into the refluxing first mixture was added 6.11 grams (0.021 moles)Dibromantin (1,3-dibromo-Δ5,5-dimethylhydantoin) as a brominating agentto form a second mixture. The second mixture gradually turned orangeafter which it rapidly turned a pale white/yellow. The second mixturewas refluxed for 30 minutes, cooled to room temperature and filteredthrough a sintered glass funnel. The residue was rinsed with 50 mldichloromethane and the combined filtrate rotovapped to dryness at atemperature of less than 35° C. The residue(Δ5-androstene-3β-ol-7-bromo-17-one) is unstable to storage and was usedimmediately in step two.

(Step 2) The residue was resolubilized in 80 ml of dichloromethane in aone liter stoppered flask equipped with a magnetic stirrer and placed inan ice bath. Into the resolubilized filtrate was added 8 grams anhydrousLiBr in 320 ml ice-cold acetone to form a third mixture. The thirdmixture was shielded from light and stirred continuously for threehours. The resulting mixture containing predominantlyandrostene-3β-ol-7α-bromo-17-one was allowed to warm to room temperatureand used immediately in step three.

(Step 3) Into a 500 ml flask equipped with a magnetic stirrer was placed320 ml dichloromethane, 80 ml glacial acetic acid, and 26 grams ofsilver acetate to form a first suspension. The first suspension wasstirred continuously for 20 minutes at room temperature. The stirredfirst suspension was added under constant agitation into the thirdmixture of predominantly Δ5-androstene-3β-ol-7α-bromo-17-one to form asecond suspension. The second suspension was constantly stirred for 30minutes at room temperature after which the suspension was filteredthrough a sintered glass funnel to separate a solid residue. Thefiltered solid residue was rinsed with 100 ml dichloromethane. Thefiltrate was washed three times with 1000 ml of water, once with 1000 mlof a 5% NaHCO₃ solution, and then twice more with water. The organicmixture containing Δ5-androstene-3β-17α-diol-17-one diacetate was thenrotovapped to dryness.

(Step 4) The dried extracted solids were resolubilized in 500 mlmethanol in a one liter, triple necked flask equipped with a magneticstirrer and a reflux condenser to form a fourth mixture. The fourthmixture was placed under a N₂ atmosphere and heated under constantstirring to reflux. Into the fourth mixture was added 250 ml of a 5%aqueous solution of Na₂ CO₃ to form a fifth mixture. The fifth mixturewas refluxed under constant agitation for 45 minutes. The methanol wasrotovapped off and the aqueous fifth mixture carefully brought to a pHof 7 with an appropriate amount of glacial acetic acid. The neutralizedfifth mixture was extracted twice with 100 ml of dichloromethane. Thedichloromethane solution of Δ5-androstene-3β,7α-diol-17-one wasrotovapped to near dryness, azeotropically dried with absolute ethanol,and then azeotropically dried twice with acetone. Warm acetone was addedto the dried extracted solids until the solids were completely dissolvedto form a sixth mixture. Hexane was added to the sixth mixture until themixture began to cloud at which time crystals ofΔ5-androstene-3β-7α-diol-17-one began to form at room temperature.

A second crop of Δ5-androstene-3β-7α-diol-17one crystals was obtained bycooling the remaining sixth mixture.

The crystals melt at 187°-189° C. When recrystallized fromacetone/hexane they melt at 192°-193° C.

Example II

(Steroid 1)

Synthesis Δ5-Androstene-3β-7(αβ)-diol-17-one

Δ5-Androstene-3β-7(αβ)-diol-17-one was manufactured in accordance withthe procedure set forth in Example I except that Step 2 was eliminatedwith the dried filtrate from Step 1 simply resolubilized in the 80 ml ofdichloromethane in preparation for Step 3.

Example III

(Steroid 2)

Synthesis Δ5-Androstene-3β-ol-7,17-dione

(Step 1) Into a 50 ml flask equipped with a magnetic stirrer and a waterbath was placed 6.5 ml acetic anhydride, 23 ml acetic acid, 1.7 gramssodium acetate, and 2 grams DHEA acetate to form a first mixture. Intothe first mixture was added 2 grams chromium trioxide over a thirtyminute period to form a second mixture. The first mixture was maintainedat a constant temperature of 56°-58° C. and continuously agitated duringaddition of the chromium trioxide. The second mixture was maintained at56°-58° C. and continuously agitated for an additional hour after whichthe second mixture was cooled and slowly poured under continuousagitation into 600 ml of ice water to form a precipitate. The flocculentprecipitate was collected on a sintered glass funnel and washed withwater until no longer green. After drying in vacuo over P₂ O₅ theproduct was dissolved in hot methanol and crystallized to yieldsubstantially pure Δ5-androstene-3β-acetoxy-7,17-dione having a meltingpoint of 184°-185° C.

(Step 2) The precipitate was resolubilized in 500 ml of methanol in aone liter, triple necked, round bottom flask equipped with a magneticstirrer and reflux condenser to form a third mixture. The third mixturewas placed under a N₂ atmosphere and heated under constant agitation toreflux. Into the third mixture was added 250 ml of a 5% solution of Na₂CO₃ to form a fourth mixture. The fourth mixture was refluxed underconstant agitation for 45 minutes. The methanol was rotovapped off andthe aqueous fourth mixture carefully brought to a pH of 7 with anappropriate amount of glacial acetic acid. The neutralized fourthmixture was extracted with two 100 ml portions of dichloromethane, thetwo dichloromethane portions combined, and the dichloromethaneevaporated in vacuo. The extracted solids were then azeotropically driedfirst with absolute ethanol and then with two separate portions ofacetone. Methanol was added to the dried extracted solids until thesolids were completely dissolved to form a fifth mixture. Hexane wasadded to the fifth mixture until the mixture began to cloud at whichtime crystals of Δ5-androstene-3β-ol-7,17 dione formed at roomtemperature.

A second crop of Δ5-androstene-3β-ol-7,17-dione crystals was obtained bycooling the remaining sixth mixture.

The resultant product had a melting point of 235°-238° C.

Example IV

(Steroid 3 )

Synthesis Δ5-Androstene-3β,7α,17β-triol

(Step 1) Into a two liter round bottom flask equipped with a magneticstirrer and a reflux condenser was placed 1000 ml hexane (b.p 69°-71°),10 grams (0.03 moles) Δ5-androstene-3β-17β-diol diacetate and 13.6 grams(0.16 moles) NaHCO₃ to form a first mixture. The first mixture wasplaced under a N₂ atmosphere and heated under constant agitation toreflux. Into the refluxing first mixture was added 6.11 g (0.021 moles)Dibromantin (1,3-dibromo-5,5-dimethylhydantoin) as a brominating agentto form a second mixture. The second mixture gradually turned orangeafter which it rapidly turned a pale white/light yellow. The secondmixture was refluxed for 30 minutes, cooled to room temperature, andfiltered through a sintered glass funnel. The residue was rinsed with 50ml dichloromethane and rotovapped to dryness at a temperature of lessthan 35° C. The dry filtrate (Δ5-androstene-3β-17β-diol-7-bromide) isunstable to storage and was used immediately in step two.

(Step 2) The dried filtrate was resolubilized in 80 ml ofdichloromethane in a flask equipped with a magnetic stirrer and placedin an ice bath. Into the resolubilized filtrate was added 8 gramsanhydrous LiBr in 320 ml ice-cold acetone to form a third mixture. Thethird mixture was shielded from light and stirred continuously for threehours. The resulting mixture of predominantlyΔ5-androstene-3β-17β-diol-7α-bromide was allowed to warm to roomtemperature and used immediately.

(Step 3) Into a 500 ml flask equipped with a magnetic stirrer was placed320 ml methylene chloride, 80 ml glacial acetic acid, and 26 gramssilver acetate to form a first suspension. The first suspension wasstirred continuously for 20 minutes at room temperature. The stirredfirst suspension was added under constant agitation to the third mixtureof predominantly Δ5-androstene-3β-17β-diol-7α-bromide to form a secondsuspension. The second suspension was constantly stirred for 30 minutesat room temperature during which the suspension gradually darkened andwas then filtered through a sintered glass funnel. The residual solidsretained on the glass filter were rinsed with 10 ml dichloromethane. Thefiltrate was washed three times with 1000 ml of water, neutralized with1000 ml of a 5% NaHCO₃ solution, and then washed twice more with water.The resulting organic mixture containingΔ5-androstene-3β,7α,17β-triol-3,17-diacetate was then rotovapped todryness.

(Step 4) The dried extracted solids were resolubilized in 500 mlmethanol within in a one liter, triple necked, round bottom flaskequipped with a magnetic stirrer and a reflux condenser to form a fourthmixture. The fourth mixture was placed under a N₂ atmosphere and heatedunder constant agitation to reflux. Into the fourth mixture was added250 ml of a 5% aqueous solution of Na₂ CO₃ to form a fifth mixture. Thefifth mixture was refluxed under constant agitation for 45 minutes. Themethanol was rotovapped off and the aqueous fifth mixture carefullybrought to a pH of 7 with an appropriate amount of glacial acetic acid.The neutralized fifth mixture was extracted twice with 100 mldichloromethane and the combined extract evaporated in vacuo. Theextracted solids (Δ5-androstene-3β,7α,17β-triol) were azeotropicallydried with absolute ethanol and then twice with acetone. Warm acetonewas added to the dried extracted solids until the solids were completelydissolved to form a sixth mixture. Hexane was added to the sixth mixtureuntil the mixture began to cloud, at which time crystals ofΔ5-androstene-3β,7α,17β-triol formed at room temperature.

A second crop of Δ5-androstene-3β,7α,17β-triol crystals was obtained bycooling the remaining sixth mixture.

Example V

(Steroid 3 )

Synthesis Δ5-Androstene-3β,7(αβ),17β-triol

Δ5-Androstene-3β,7(αβ),17β-triol was manufactured in accordance with theprocedure set forth in Example IV except that Step 2 was eliminated withthe dried filtrate from Step 1 simply resolublized in the 80 ml ofmethylene chloride in preparation for Step 3.

Example VI

(Steroid 4)

Synthesis Δ5-Androstene-3β,17β-diol-7-one

(Step 1) Into a 50 ml flask equipped with a magnetic stirrer and a waterbath was placed 6.5 ml acetic anhydride, 23 ml acetic acid, 1.7 gramssodium acetates and 2 grams androstenediol diacetate to form a firstmixture. Into the first mixture was added 2 grams chromium trioxide overa thirty minute period to form a second mixture. The first mixture wasmaintained at a constant temperature of 56°-58° C. and continuouslyagitated during addition of the chromium trioxide. The second mixturewas maintained at 56°-58° C. and continuously agitated for an additionalhour after which the second mixture was cooled and slowly poured withcontinuous agitation into 600 ml of ice water to form a precipitate. Theflocculent precipitate was filtered through a sintered glass funnel,washed with water until no longer green, and dried in vacuo.

(Step 2) The dried precipitate was resolubilized in 500 ml of methanolin a one liter, round bottom flask equipped with a magnetic stirrer andreflux condenser to form a third mixture. The third mixture was placedunder a N₂ atmosphere and heated under constant agitation to reflux.Into the third mixture was added 250 ml of a 5% aqueous solution of Na₂CO₃ to form a fourth mixture. The fourth mixture was refluxed underconstant agitation for 45 minutes. The methanol was rotovapped off andthe aqueous fourth mixture carefully brought to a pH of 7 with anappropriate amount of glacial acetic acid. The neutralized fourthmixture was extracted twice with 100 ml portions of dichloromethane andthe combined dichloromethane extract evaporated in vacuo. The extractedsolids were then azeotropically dried first with absolute ethanol andthen twice with acetone. Methanol was added to the dried extractedsolids until the solids were completely dissolved to form a fifthmixture. Hexane was added to the fifth mixture until the mixture beganto cloud at which time crystals of Δ5-androstene-3β,17β-diol-7-oneformed at room temperature.

The resultant product had a melting point of 200°-202° C.

Example VII

(Steroid 5)

Synthesis Δ5-Androstene-3β-acetoxy-7,16,17-trione

(Step 1) Into a 50 ml flask equipped with a magnetic stirrer and a waterbath was placed 6.5 ml acetic anhydride, 23 ml acetic acid, 1.7 gramssodium acetate, and 2 grams DHEA acetate to form a first mixture. Intothe first mixture was added 2 grams chromium trioxide over a thirtyminute period to form a second mixture. The first mixture was maintainedat a constant temperature of 56°-58° C. and continuously agitated duringaddition of the chromium trioxide.

(Step 2) The second mixture was maintained at 56°-58° C. andcontinuously agitated for an additional hour after which the secondmixture was cooled and slowly poured under continuous agitation into 600ml of ice water to form a precipitate. The flocculent precipitate wascollected on a sintered glass funnel and washed with water until nolonger green. After drying in vacuo over P₂ O₅, the product wasdissolved in methanol and recrystallized to yield substantially pure3β-acetoxy-Δ5-androstene-7,17-dione (51) having a melting point of184°-185° C.

(Step 3) Into a second 50 ml round bottom flask equipped with a magneticstirrer and retained within a dry-ice bath was placed 1.00 gram (2.90mmoles) of the 3β-acetoxy-Δ5-androstene-7,17-dione (51) and 20 ml neattetrahydrofuran to form a third mixture, The third mixture was placedunder a N₂ atmosphere. Into the third mixture was added 1.07 ml (8.43mmoles) trimethylchlorosilane to form a fourth mixture. The fourthmixture was maintained under the N₂ atmosphere and cooled to -78° C.

(Step 4) Into a third 25 ml round bottom flask equipped with a magneticstirrer and retained within a dry-ice bath was placed 1.07 ml (7.66mmoles) diisopropyl amine, 3.60 ml of a 1.94M solution of n-butyllithiumin hexane (6.96 mmoles), and 4 ml of tetrahydrofuran to form lithiumdiisopropyl amide. The solution (LDA solution) was prepared under a N₂atmosphere at -78° C. The LDA solution was warmed slightly to dissolveany solids therein and then added, under a N₂ atmospheres to the fourthmixture via cannula to form a fifth mixture.

(Step 5) The fifth mixture was removed from the dry-ice bath and allowedto warm to room temperature for 15 minutes at which time 1.25 mltriethylamine was added to the fifth mixture to form a sixth mixture.Into a separatory funnel was placed 40 ml hexane, 40 ml of a saturatedNaHCO₃ aqueous solution, and the sixth mixture. The organic phase wasextracted with hexane, washed with a saturated NaCl aqueous solution,dried over Na₂ SO₄ and the solvent removed to yield 1.42 grams of a dryorganic solid. The organic solid was identified by NMR (CDCl₃) as anapproximately 70:30 mixture of3β-(trimethylsilyl)acetoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-onetrimethylsilyl ether (52b) and3β-acetoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-one trimethylsilyl ether(52a). The results of the NMR analysis are set forth in Tables One &Two.

(Step 6) Into a fourth 100 ml round bottom flask equipped with amagnetic stirrer and retained within a dry-ice bath was placed 2.85moles of the organic solid obtained in Step 5, 20 ml neattetrahydrofuran and 0.320 ml (4.00 mmole) neat pyridine to form aseventh mixture. The seventh mixture was cooled to -78° C. and placedunder a N₂ atmosphere. Into the seventh mixture was added 0.710 grams(3.71 moles) of benzeneselenenyl chloride in 4 ml of tetrahydrofuran toform an eighth mixture.

(Step 7) Into a separatory funnel was placed a cosolvent system of a 0.5N HCl aqueous solution and dichloromethane. Into the cosolvent systemwas added the eighth mixture to extract the organic phase. The secondorganic phase was extracted by dichloromethane, sequentially washed withwater and a saturated NaHCO₃ aqueous solution, dried over Na₂ SO₄ andthe solvent removed to yield 1.72 grams of an organic oil. The organicoil was separated by chromatography (100 grams silica eluted withhexane-ethyl acetate at 90:10 to 50:50 with 50 ml fractions) into 1.44grams of first and second organic fractions (Fractions 14-17), diphenyldiselenide (Fractions 9-11) and unreactedacetoxy-Δ5-androstene-7,17-dione (51) (Fractions 18-19). The first andsecond organic fractions were identified by NMR as3β-acetoxy-16*-phenylseleno-Δ5-androstene-7,17-dione (53a) and3β-(trimethylsilyl)acetoxy-16-phenylseleno-Δ5-androstene-7,17-dione(53b) respectively. The results of the NMR analysis are set forth inTables Three and Four.

(Step 8) Into a fifth 100 ml round bottom flask equipped with a magneticstirrer was placed 25 ml ether, 5 ml dichloromethane and 1.19 mmoles ofthe second organic fraction obtained in Step 7 (53b) to form a ninthmixture. Into the ninth mixture was added 8 ml of a 10% aqueous solutionof potassium fluoride and 3 ml of a 1M tetra-n-butylammonium fluoridesolution in tertrahydrofuran to form a tenth mixture. The tenth mixturewas maintained at 25° C. and continuously agitated for two hours afterwhich the tenth mixture was poured into an ether-hexane-water solventsystem to extract the organic phase. The extracted organic phase waswashed twice with water, once with a saturated NaCl aqueous solution,dried over Na₂ SO₄ and the solvent removed to yield 0.594 grams of3β-acetoxy-16-phenylseleno-Δ5-androstene-7,17-dione (53a).

(Step 9) Into a sixth 100 ml round bottom flask equipped with a magneticstirrer was placed 25 ml dichloromethane and 1.10 mmoles of3β-acetoxy-16-phenylseleno-Δ5-androstene-7,17-dione (53a) to form aneleventh mixture. The eleventh mixture was cooled to 0° C. andmaintained under continuous agitation. Into the eleventh mixture wasadded 0.296 grams (1.2 mmoles) m-chloroperbenzoic acid (70%) followedfive minutes later by 0.40 ml dimethylsulfide to form a thirteenthmixture. The thirteenth mixture was washed 3 times with 50 ml of a coldNaHCO₃ aqueous solution and filtered through Na₂ SO₄.

(Step 10) Into a seventh 250 ml round bottom flask equipped with amagnetic stirrer was placed 1.2 ml acetic anhydride, 1.2 ml pyridine andthe liquid phase of the thirteenth mixture to form a fourteenth mixture.The fourteenth mixture was continuously agitated at room temperature foran hour after which 60 ml of a saturated NaHCO₃ aqueous solution wasadded to form a fifteenth mixture having separate organic and inorganiclayers. The fifteenth mixture was maintained under continuous agitationuntil bubbling ceased. The organic layer was separated from theinorganic layer by drawing off the organic layer in a separatory funnel.The separated organic layer was washed with a saturated NaHCO₃ aqueoussolution, dried over Na₂ SO₄ and the solvent removed to yield 0.713grams of a dry organic solid. The organic solid was identified by NMR(CDCl₃) as a 90:10 mixture of3β,16-diacetoxy-16-phenylseleno-Δ5-androstene-7,17-dione (55) and3β-acetoxy-Δ5-androstene-16-phenylseleno-16-m-chlorobenzoate-7,17-dione(54). The results of an NMR analysis of the (55) fraction in the mixtureare set forth in Table Five.

(Step 11) Into a round bottom flask equipped with a magnetic stirrer wasplaced 25 ml carbon tetrachloride and 1.10 mmoles of the 90:10 mixtureof 3β,16-diacetoxy-16-phenylseleno-Δ5-androstene-7,17-dione (55) and3β-acetoxy-Δ5-androstene-16-phenylseleno-16-m-chlorobenzoate-7,17-dione(54) to form a sixteenth mixture. Into the sixteenth mixture was added0.12 ml pyridine, 10 mg benzeneseleninic acid, and 19 mgdiphenyldiselenide to form a seventeenth mixture. The seventeenthmixture was maintained under vigorous agitation and 3.4 ml of a 15% H₂O₂ aqueous solution added to form an eighteenth mixture. The eighteenthmixture was agitated continuously for 45 minutes after which theeighteenth mixture was washed twice with a saturated NaHCO₃ aqueoussolution and dried in vacuo to yield 0.390 grams of an organic solid.The organic solid was separated by chromatography (50 grams silica geleluted with 50% hexane-ethyl acetate with 25 ml fractions) to yield0.236 grams of an organic fraction (Fractions 9-10). The organicfraction was identified by NMR as pure3β,16-diacetoxy-Δ5,Δ15-androstadiene-7,17-dione (57). The results of theNMR analysis are set forth in Table Six.

(Step 12) Into a round bottom flask equipped with a magnetic stirrer wasplaced 1.03 mmoles of 3β,16-diacetoxy-Δ5,Δ15-androstadiene-7,17-dione(57) and 15 ml methanol to form a nineteenth mixture. Into thenineteenth mixture was placed 0.500 ml triethylamine to form a twentiethmixture. The twentieth mixture was placed under a N₂ atmosphere andmaintained under constant agitation for 16 hours. The twentieth mixturewas then extracted between H₂ O and CH₂ Cl₂. The organic layer waswashed twice with a saturated NaHCO₃ aqueous solution, and then driedand evaporated under reduced pressure to yield 0.281 grams of a yelloworganic solid. The organic solid was identified by NMR as a mixture oforganic compounds including about 65%3β-acetoxy-Δ5-androstene-7,16,17-trione (5). The results of the NMRanalysis are set forth in Table Seven.

Example VIII

(Steroid 6)

Synthesis 3β,16α-dihydroxy-Δ5-androstene-7,17-dione

(Step 1) Into a round bottom flask equipped with a magnetic stirrer wasplaced 2.80 mmoles of3β-propionoxy-17-hydroxy-Δ5,Δ16-androstadiene-7-one trimethylsilyl ether(62) synthesized in accordance with the procedure set forth in ExampleVII and identified by NMR (See Table Nine) and 40 ml of tetrahydrofuranto form a first mixture which was cooled to 0° in an ice bath. Into thefirst mixture was placed 2.95 mmoles of m-chloroperbenzoic acid (80-90%)to form a second mixture. The second mixture was warmed to 25° C. andmaintained under constant agitation for 10 min.

(Step 2) The second mixture was continuously agitated and 40 ml of a 1NHCl aqueous solution added to form a third mixture which was maintainedunder constant agitation for 20 min. The third mixture was partitionedbetween ether and water and separated by decanting the ether phase fromthe water phase. The ether phase was washed with a saturated NaHCO₃aqueous solution, then a saturated NaCl aqueous solution, and dried invacuo to yield an organic solid. The organic solid was purified bychromatography (140 gm of silica eluted with 60:40 to 70:30 ethylacetate-hexane with 25 ml fractions) to give 0.586 gm of a first organiccompound. The first organic compound was identified by NMR as3β-propionoxy-16α-hydroxy-Δ5-androstene-7,17-dione (63). The results ofthe NMR analysis are set forth in Table Ten.

(Step 3) In a second round bottom flask equipped with a magnetic stirrerwas placed 0.155 mmoles of3β-propionoxy-16α-hydroxy-Δ5-androstene-7,17-dione (63) dissolved in 6ml of methanol to form a third mixture. To this third mixture was added1.5 ml of an aqueous solution of 6N sulfuric acid to form a fourthmixture which was maintained at 25° C. for 18 hours. The fourth mixturewas then partitioned between ethyl acetate and water and separated bydecanting the ethyl acetate phase from the water phase. The ethylacetate was evaporated to yield an organic product which was purified bychromatography (silica preparative plate eluted three times with 60%ethyl acetate-hexane) to yield 18 mg of an organic compound which wasthen dissolved in and crystallized from methanol to give 6 mg ofsubstantially pure material having a melting point of 235°-239° C. Theorganic compound was identified by NMR as3β,16α-dihydroxy-Δ5-androstene-7,17-dione (6). The results of the NMRanalysis are set forth in Table Eleven.

Example IX

(Steroid 7)

Synthesis Δ5-Androstene-3β-propionoxy-16β-acetoxy-7,17-dione

(Step 1) Into a round bottom flask equipped with a magnetic stirrer wasplaced 1.52 mmoles of3β-propionoxy-16α-hydroxy-Δ5-androstene-7,17-dione, 3.0 mmoles oftriphenylphosphine, 6.0 mmoles of acetic acid in 11 ml oftetrahydrofuran. This first mixture was placed under N₂ and cooled to 0°C. in an ice bath. To the first mixture was added 3.0 mmoles of diethylazodicarboxylate dropwise to form a second mixture. The second mixturewas warmed to 25° C. and maintained at this temperature for 18 hr. Itwas then partitioned between ether-hexane and water. The ether-hexanelayer was washed with waters water, saturated NaHCO₃ aqueous solution,saturated NaCl aqueous solution, dried over Na₂ SO₄ and evaporated togive an organic solid which was purified by chromatography on 130 gmsilica eluted with ethyl acetate-hexane (20:80 to 50:50) with 25 mlfractions and crystallized from dichloromethane-hexane to yield 0.267 gmof an organic compound. The organic compound was identified by NMR as3β-propionoxy-16β-acetoxy-Δ5-androstene-7,17-dione containing ˜20% ofthe 16α epimer. The results of the NMR analysis are set forth in TableTwelve.

(Step 2) Conversion to Δ5-androstene-3β,16β-dihydroxy-7,17-dione can bedone as described in Example VIII.

Example X

(Steroid 8)

Synthesis Δ5-Androstene-3β,7α,17β-triol-16-one

(Step 1) Into a 100 ml round bottomed flask was placed 3 grams (7.7mmoles) of 3β,16α-diacetoxy DHEA (prepared in accordance with theprocedure set forth in Numazawa, M. and Osawa, Y. Steroids, vol. 32, p519 (1978)) and 3.5 grams NaHCO₃ in 50 ml of hexane to form a firstmixture, The first mixture was stirred and heated to reflux under a N₂atmosphere. To the first mixture was added 1.6 grams dibromantin(1,3-dibromo-5,5-dimethylhydantoin) to form a second mixture.

(Step 1) The second mixture was stirred, refluxed for 30 minutes, andthen cooled to room temperature. The refluxed second mixture wasfiltered to remove solids and washed with CH₂ Cl₂. The resultantfiltrate was concentrated to near dryness in vacuo using a water bathmaintained below 35° C.

(Step 3) The dried filtrate was resolubilized in 21 ml of toluene in aone liter stoppered flask equipped with a magnetic stirrer and placed inan ice bath. Into the resolubilized filtrate was added 2.1 gramsanhydrous LiBr in 80 ml ice-cold acetone to form a third mixture. Thethird mixture was shielded from light and stirred continuously for threehours at 0° C. The resulting mixture containing predominantly 7α-bromowas used immediately in step four.

(Step 4) Into a 500 ml flask equipped with a magnetic stirrer was placed80 ml dichloromethane, 21 ml glacial acetic acid, and 6.7 grams ofsilver acetate to form a first suspension. The first suspension wasstirred continuously for 20 minutes at room temperature. The stirredfirst suspension was added under constant agitation into the warmedthird mixture to form a second suspension. The second suspension wasconstantly stirred for 30 minutes at room temperature after which thesuspension was filtered through a sintered glass funnel to separate asolid residue. The filtrate was concentrated to yield an oily residue.

(Step 5) To the oily residue was added 300 ml H₂ O and sufficient NaHCO₃to achieve a fourth mixture with a neutral pH. The fourth mixture wasextracted five times with 150 ml of ethyl acetate, the organic layerscombined, washed with brine, dried over MgSO₄ and concentrated todryness.

(Step 6) The crude organic phase was separated by chromatography (silicagel eluted with ethyl acetate: pet ether at 1:3, 1:2 and 1:1) to yield700 mg (20%) of a first organic fraction and 1.5 grams (48%) of a secondorganic fraction. After crystallization from diethyl ether the first (mp170°-172° C.) and second (mp 155°-158° C.) organic fractions wereidentified by NMR as Δ5-androstene-3β,7α,16α-triacetoxy-17-one and thecorresponding Δ5-androstene-3β,16α-diacetoxy-7α-ol-17-one (83)respectively. The results of the NMR analysis of these two compounds areset forth in Tables Thirteen and Fourteen.

(Step 7) Into a flask equipped with a magnetic stirrer was added 400 mg(1 mmole) of the Δ5- Androstene-3β,16α-diacetoxy-7α-hydroxy-17-one (83)and 342 mg of K₂ CO₃ in 25 ml of methanol at room temperature to form afifth mixture. The fifth mixture was stirred for two hours. The alkalinesolution enolized the 17-keto to form the more stable 17-hydroxy-16-onecompound. Δ5-Androstene-3β,7α,17-trihydroxy-16-one (8) was isolated fromthe fifth mixture by filtering to remove the insoluble salts evaporatingthe methanol in vacuo, purifying the organic residue over silica gel andcrystallizing the organic compound from methanol-ethyl ether solution.The crystallized organic fraction (180 mg, 56%; mp:>230° C.) wasidentified by NMR as Δ5-androstene-3β,7α,17-trihydroxy-16-one (8). Theresults of the NMR analysis are set forth in Table Fifteen.

Example XI

(Steroid 9)

Synthesis Δ5-Androstene-3β,17β-diol-7,16-dione

(Step 1) Into a round bottom flask equipped with a magnetic stirrer wasadded 1.05 grams (2.80 mmoles)Δ5-androstene-3β-propionoxy-16α-hydroxy-7,17-dione (63), 80 ml methanoland 40 ml of a 5% aqueous Na₂ CO₃ solution while stirring rapidly toform a first mixture. The first mixture was stirred for 42 hours afterwhich the methanol was evaporated and a combination of 100 ml of waterand 2 ml of acetic acid added to form a second mixture. A solid materialwas filtered from the second mixture, resolubilized in methanol and thencrystalized to yield 0.324 gm of an organic compound.

A small sample of the organic compound was again recrystalized frommethanol to produce a purified sample having a melting point of215°-218° C. The first organic compound was identified by NMR asandrostene-3β,17β-diol-7,16-dione. The results of the NMR analysis areset forth in Table Sixteen.

                  TABLE ONE                                                       ______________________________________                                        NMR Results                                                                   3β-acetoxy-17-hydroxy-.increment.5,.increment.16-androstadiene-          7-one-trimethylsilyl ether (52a)                                              Conditions Peak         Significance                                          ______________________________________                                        (δ) CDCl.sub.3                                                                     0.21         s, O--SiMe.sub.3                                      270 MHz                                                                                  0.87         s, 18-CH.sub.3                                                   1.25         s, 19-CH.sub.3                                                   2.07         s, CH.sub.3 COO                                                  2.75         ddd, J=14, 6, 3, Hz                                                           15α-H                                                      4.54         dd, J=3, 1.5 Hz                                                               16-H                                                             4.73         tt, J=11, 5 Hz                                                                3α-H                                                       5.76         d, J=2 Hz                                                                     6-H                                                   ______________________________________                                    

                  TABLE TWO                                                       ______________________________________                                        NMR Results                                                                   3β-(trimethylsilyl)acetoxy-17-hydroxy-                                   .increment.5,.increment.16-androstadiene-7-one trimethylsilyl ether           (52b)                                                                         Conditions Peak         Significance                                          ______________________________________                                        (δ) CDCl.sub.3                                                                     0.13         s, C--SiMe.sub.3                                      270 MHz                                                                                  0.21         s, O--SiMe.sub.3                                                 0.87         s, 18-CH.sub.3                                                   1.25         s, 19-CH.sub.3                                                   1.90         s, CH.sub.2 --Si                                                 2.75         ddd, J=14, 6, 3, Hz                                                           15α-H                                                      4.54         dd, J=3, 1.5 Hz                                                               16-H                                                             4.73         tt, J=11, 5 Hz                                                                3α-H                                                       5.76         d, J=2 Hz                                                                     6-H                                                   ______________________________________                                    

                  TABLE THREE                                                     ______________________________________                                        NMR Results                                                                   3β-acetoxy-16α-phenylseleno-                                       .increment.5-androstene-7,17-dione (53a)                                      Conditions Peak          Significance                                         ______________________________________                                        (δ) CDCl.sub.3                                                                     0.92          s, 18-CH.sub.3                                       270 MHz                                                                                  1.21          s, 19-CH.sub.3                                                  2.07          s, CH.sub.3 COO                                                 3.00          ddd, J=14, 5, 0.5                                                             Hz                                                                            15α-H                                                     4.10          d, J=7.5 Hz                                                                   J.sub.SeH =5 Hz                                                               16β-H                                                      4.73          tt, J=11, 5 Hz                                                                3α-H                                                      5.74          d, J=1.5 Hz                                                                   6-H                                                             7.31          m, SePh                                                         7.68          m, SePh                                              ______________________________________                                    

                  TABLE FOUR                                                      ______________________________________                                        NMR Results                                                                   3β-(trimethylsilyl)acetoxy-16α-phenylseleno-                       .increment.5-androstene-7,17-dione (53b)                                      Conditions  Peak           Significance                                       ______________________________________                                        (δ) CDCl.sub.3                                                                      0.13           s, C--SiMe.sub.3                                   200 MHz                                                                                   0.91           s, 18-CH.sub.3                                                 1.21           s, 19-CH.sub.3                                                 1.91           s, CH.sub.2 Si                                                 3.00           ddd, J=14                                                                     5.5, 0.5 Hz                                                                   15α-H                                                    4.10           d, J=7.5 Hz                                                                   J.sub.SeH =5 Hz                                                               16β-H                                                     4.73           tt, J=10.5 Hz                                                                 3α-H                                                     5.74           d, J=1.5 Hz                                                                   6-H                                                            7.32           m, SePh                                                        7.68           m, SePh                                            ______________________________________                                    

                  TABLE FIVE                                                      ______________________________________                                        NMR Results                                                                   3β,16-diacetoxy-.increment.5-androstene-                                 16-phenylseleno-7,17-dione (55)                                               Conditions Peak          Significance                                         ______________________________________                                        (δ) CDCl.sub.3                                                                     1.25          s, 18-CH.sub.3                                       200 MHz                                                                                  1.35          s, 19-CH.sub.3                                                  2.05          s, 3-CH.sub.3 COO                                               2.09          s, 16-CH.sub.3 COO                                              3.20          dd, J=14.5, 6 Hz                                                              15α-H                                                     4.73          tt, J=11, 5.5 Hz                                                              3α-H                                                      5.74          d, J=1.5 Hz                                                                   6-H                                                             7.35          m, SePh                                                         7.68          m, SePh                                              ______________________________________                                    

                  TABLE SIX                                                       ______________________________________                                        NMR Results                                                                   3β,16-diacetoxy-,.increment.5,.increment.15-androstadiene-               7,17-dione (57)                                                               Conditions  Peak          Significance                                        ______________________________________                                        (δ) CDCl.sub.3                                                                      1.24          s, 18-CH.sub.3                                      200 MHz                                                                                   1.30          s, 19-CH.sub.3                                                  2.07          s, 3-CH.sub.3 COO                                               2.25          s, 16-CH.sub.3 COO                                              4.75          tt, J=11, 5 Hz                                                                3α-H                                                      5.83          d, J=1.5 Hz                                                                   6-H                                                             7.82          broad s, 15-H                                       ______________________________________                                    

                  TABLE SEVEN                                                     ______________________________________                                        NMR Results                                                                   3β-acetoxy-.increment.5-androstene-7,16,17-trione (5)                    Conditions Peak          Significance                                         ______________________________________                                        (δ) CDCl.sub.3                                                                     1.07          s, 18-CH.sub.3                                       270 MHz                                                                                  1.30          s, 19-CH.sub.3                                                  2.05          s, 3-CH.sub.3 COO                                               2.44          dd, J=18.5, 8 Hz                                                              15β-H                                                      2.61          m, 4-H                                                          3.43          dd, J=18.5,                                                                   6.5 Hz                                                                        15α-H                                                     4.75          tt, J=11, 5 Hz                                                                3α-H                                                      5.80          d, J=1.5 Hz                                                                   6-H                                                  ______________________________________                                    

                  TABLE EIGHT                                                     ______________________________________                                        NMR Results                                                                   3β-propionoxy-.increment.5-androstene-7,17-dione (61)                    Conditions  Peak          Significance                                        ______________________________________                                        (δ) CDCl.sub.3                                                                      0.91          s, 18-CH.sub.3                                      270 MHz                                                                                   1.16          t, J=7.5 Hz                                                                    .sub.----CH.sub.3 CH.sub.2 COO                                 1.25          s, 19-CH.sub.3                                                  2.15          dt, J=19, 8.5 Hz                                                              16α-H                                                     2.33          q, J=7.5 Hz                                                                   CH.sub.3 .sub.----CH.sub.2 COO                                  2.83          dddd, J=15.5,                                                                 8.5, 4, 1 Hz                                                                  15α-H                                                     4.75          tt, J=11, 5 Hz                                                                3α-H                                                      5.77          d, J=2 Hz                                                                     6-H                                                 ______________________________________                                    

                  TABLE NINE                                                      ______________________________________                                        NMR Results                                                                   3β-propionoxy-17-hydroxy-,.increment.5,.increment.16-                    androstadiene-7-one trimethylsilyl ether (62)                                 Conditions  Peak          Significance                                        ______________________________________                                        (δ) CDCl.sub.3                                                                      0.18          s, Si--Me.sub.3                                     270 MHz                                                                                   0.85          s, 18-CH.sub.3                                                  1.13          t, J=7.5 Hz                                                                    .sub.----CH.sub.3 CH.sub.2 COO                                 1.21          s, 19-CH.sub.3                                                  2.14          ddd, J=14.8,                                                                  10.7, 1.5 Hz                                                                  15β-H                                                      2.31          q, J=7.5 Hz                                                                   CH.sub.3 .sub.----CH.sub.2 COO                                  2.71          ddd, J=14.8,                                                                  6.4, 2.1 Hz                                                                   15α-H                                                     4.52          dd, J=3.1, 1.5                                                                Hz                                                                            16-H                                                            4.72          tdd, J=11.4,                                                                  5.3, 4.4 Hz                                                                   3α-H                                                      5.71          d, J=1.6 Hz                                                                   6-H                                                 ______________________________________                                    

                  TABLE TEN                                                       ______________________________________                                        NMR Results                                                                   3β-propionoxy-16α-hydroxy-.increment.5-                            androstene-7,17-dione (63)                                                    Conditions  Peak          Significance                                        ______________________________________                                        (δ) CDCl.sub.3                                                                      1.00          s, 18-CH.sub.3                                      270 MHz                                                                                   1.15          t, J=7.5 Hz                                                                    .sub.----CH.sub.3 CH.sub.2 COO                                 1.23          s, 19-CH.sub.3                                                  2.33          q, J=7.5 Hz                                                                   CH.sub.3 .sub.----CH.sub.2 COO                                  2.75          ddd, J=13.5,                                                                  6.5, 1.5 Hz                                                                   15α-H                                                     4.42          d, J=8 Hz                                                                     16β-H                                                      4.76          tt, J=10.5, 4.5                                                               Hz                                                                            3α-H                                                      5.77          d, J=1.5 Hz                                                                   6-H                                                 ______________________________________                                    

                  TABLE ELEVEN                                                    ______________________________________                                        NMR Results                                                                   3β,16α-dihydroxy-                                                  .increment.5-androstene-7,17-dione (6)                                        Conditions Peak          Significance                                         ______________________________________                                        (δ) CDCl.sub.3                                                                     1.00          s, 18-CH.sub.3                                       270 MHz                                                                                  1.23          s, 19-CH.sub.3                                                  2.26          ddd, J=14.5,                                                                  10.5, 8.6 Hz                                                                  15β-H                                                      2.55          ddd, J=14.1,                                                                  5.0, 1.3 Hz                                                                   4α-H                                                      2.76          ddd, J=14.6, 6.9                                                              1.4 Hz                                                                        15α-H                                                     3.69          broad t, J=11 Hz                                                              3α-H                                                      4.41          d, J=8.5 Hz                                                                   16β-H                                                      5.75          d, J=1.7 Hz                                                                   6-H                                                  ______________________________________                                    

                  TABLE TWELVE                                                    ______________________________________                                        NMR Results                                                                   3β-propionoxy-16β-acetoxy-.increment.5-                             androstene-7,17-dione (7)                                                     Conditions  Peak          Significance                                        ______________________________________                                        (δ) CDCl.sub.3                                                                      1.00          s, 18-CH.sub.3                                      270 MHz                                                                                   1.15          t, J=7.5 Hz                                                                    .sub.----CH.sub.3 CH.sub.2 COO                                 1.25          s, 19-CH.sub.3                                                  2.12          s, CH.sub.3 COO                                                 2.33          q, J=7.5 Hz                                                                   CH.sub.3 .sub.----CH.sub.2 COO                                  3.35          ddd, J=11, 8.5                                                                4 Hz                                                                          15α-H                                                     4.74          tt, J=11, 4 Hz                                                                3α-H                                                      5.77          d, J=1.5 Hz                                                                   6-H                                                 ______________________________________                                    

                  TABLE THIRTEEN                                                  ______________________________________                                        NMR Results                                                                   .increment.5-Androstene-3β,16α-diacetoxy-                          7α-hydroxy-17-one (83)                                                  Conditions  Peak          Significance                                        ______________________________________                                        (δ) CDCl.sub.3                                                                      0.98          s, CH.sub.3                                         300 MHz                                                                                   1.02          s, CH.sub.3                                                     2.02          s, 2xCO.sub.2 CH.sub.3                                          2.10          s, CO.sub.2 CH.sub.3                                            4.70          m, 1H, 3-H                                                      5.02          dd, 1H, J=2 Hz                                                                7-H                                                             5.40          d, 1H, J=4 Hz                                                                 16-H                                                            5.61          d, 1H, J=2 Hz                                                                 6-H                                                 ______________________________________                                    

                  TABLE FOURTEEN                                                  ______________________________________                                        NMR Results                                                                   .increment.5-androstene-3β,16α-diacetoxy-                          7α-ol-17-one                                                            Conditions  Peak          Significance                                        ______________________________________                                        (δ) CDCl.sub.3                                                                      0.97          s, CH.sub.3                                         300 MHz                                                                                   1.02          s, CH.sub.3                                                     2.04          s, CO.sub.2 CH.sub.3                                            2.15          s, CO.sub.2 CH.sub.3                                            3.92          m, 1H, 7-H                                                      4.63          m, 1H, 3-H                                                      5.44          d, 1-H, J=5 Hz                                                                16-H                                                            5.64          d, 1-H, J=4 Hz                                                                6-H                                                 ______________________________________                                    

                  TABLE FIFTEEN                                                   ______________________________________                                        NMR Results                                                                   .increment.5-androstene-3β,7α,17-trihydroxy-16-one (8)             Conditions  Peak          Significance                                        ______________________________________                                        (δ) DMSO                                                                            0.61          s, CH.sub.3                                         300 MHz                                                                                   0.92          s, CH.sub.3                                                     3.32          m, 3-H                                                          3.60          broad s                                                                       1H, 7-H                                                         3.64          s, 1H, 16-H                                                     4.26          d, 1H, J=2 Hz                                                                 OH, D.sub.2 O exch.                                             4.68          broad s, 1H                                                                   OH, D.sub.2 O exch.                                             5.30          broad s, 1H                                                                   OH, D.sub.2 O exch.                                             5.42          d, 1H, J=2 Hz                                                                 6-H                                                 ______________________________________                                    

                  TABLE SIXTEEN                                                   ______________________________________                                        NMR Results                                                                   3β,17β-dihydroxy-,.increment.5-                                     androstene-7,16-dione (9)                                                     Conditions  Peak          Significance                                        ______________________________________                                        (δ) CDCl.sub.3                                                                      0.75          s, 18-CH.sub.3                                      270 MHz                                                                                   1.26          s, 19-CH.sub.3                                                  3.15          ddd, J=19, 7,                                                                 1.5 Hz                                                                        15α-H                                                     3.72          tt, J=10, 4.5 Hz                                                              3α-H                                                      3.78          broad s                                                                       17α-H                                                     5.77          d, J=1.5 Hz                                                                   6-H                                                 ______________________________________                                    

We claim:
 1. A biologically active steroid effective for promotingweight control without suppressing appetite or promoting the synthesisof sex hormones comprising Δ 5-androstene-3β-acetoxy-7,16,17-trione. 2.A biologically active steroid effective for promoting weight controlwithout suppressing appetite or promoting the synthesis of sex hormonescomprising Δ5-androstene-3β,16α-dihydroxy-7,17-dione.
 3. A biologicallyactive steroid effective for promoting weight control withoutsuppressing appetite or promoting the synthesis of sex hormonescomprising Δ5-androstene-3β-propionoxy-16β-acetoxy-7,17-dione.
 4. Abiologically active steroid effective for promoting weight controlwithout suppressing appetite or promoting the synthesis of sex hormonescomprising Δ5-androstene-3β,7α,17β-triol-16-one.
 5. A biologicallyactive steroid effective for promoting weight control withoutsuppressing appetite or promoting the synthesis of sex hormonescomprising Δ5-androstene-3β,17α-diol-7,16-dione.
 6. A biologicallyactive steroid effective for promoting weight control withoutsuppressing appetite or promoting the synthesis of sex hormonescomprising Δ5-androstene-3β,16α,17β-triol,7-one.